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- Title
Cytosine arabinoside rapidly activates Bax-dependent apoptosis and a delayed Bax-independent death pathway in sympathetic neurons.
- Authors
Besirli, C G; Deckwerth, T L; Crowder, R J; Freeman, R S; Johnson, E M, Jr
- Abstract
Cytosine arabinoside (ara-C) is a nucleoside analog used in the treatment of hematologic malignancies. One of the major side effects of ara-C chemotherapy is neurotoxicity. In this study, we have further characterized the cell death induced by ara-C in sympathetic neurons. Similar to neurons undergoing trophic factor deprivation-induced apoptosis, ara-C-exposed neurons became hypometabolic before death and upregulated c-myb, c-fos, and Bim. Bax deletion delayed, but did not prevent, ara-C toxicity. Neurons died by apoptosis, indicated by the release of mitochondrial cytochrome-c and caspase-3 activation. p53-deficient neurons demonstrated decreased sensitivity to ara-C, but neither p53 nor multiple p53-regulated genes were induced. Mature neurons showed increased ara-C resistance. These results demonstrate that molecular mechanisms underlying ara-C-induced death are similar to those responsible for trophic factor deprivation-induced apoptosis. However, substantial differences in neuronal death after these two distinct stress stimuli exist since ara-C toxicity, unlike the developmental death, can proceed in the absence of Bax.
- Publication
Cell death and differentiation, 2003, Vol 10, Issue 9, p1045
- ISSN
1350-9047
- Publication type
Journal Article
- DOI
10.1038/sj.cdd.4401259